US10028942B2ActiveUtilityA1
3-substituted pyrazoles and uses thereof
Est. expiryJan 18, 2033(~6.5 yrs left)· nominal 20-yr term from priority
A61P 43/00A61P 9/10A61P 29/00A61P 27/06A61P 27/02A61P 25/28A61P 25/16A61P 25/14A61P 25/08A61P 25/04A61P 25/02A61P 25/00A61P 21/04A61P 21/00A61P 19/00C07D 405/14A61K 31/437A61K 31/4545C07D 401/14C07D 471/04C07D 401/04A61K 31/4439
71
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1
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Claims
Abstract
In compounds of Formula I, the groups R1, R2, R3, R4, R5, R6 and R7 have the meaning as described herein. The present invention also provides for methods of using compounds of Formula I and compositions comprising compounds of Formula (I) as DLK inhibitors and for treating neurodegeneration diseases and disorders.
Claims
exact text as granted — not AI-modifiedThe invention claimed is:
1. A method for inhibiting degeneration of a central nervous system (CNS) neuron in a patient having a neurodegenerative disease or condition; or for decreasing one or more symptoms of a neurodegenerative disease or condition in a patient suffering therefrom; or for decreasing the progression of a neurodegenerative disease or condition in a patient suffering therefrom; wherein said neurodegenerative disease or condition is selected from the group consisting of: Alzheimer's disease, Huntington's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), and glaucoma; comprising administering to said patient a therapeutically effective amount of a compound of Formula (I)
or a pharmaceutically acceptable salt thereof;
wherein in Formula (I)
R 1 is selected from the group consisting of hydrogen, —F, —Cl, —Br, —I, —NO 2 , —CN, C 1-12 alkyl and C 1-12 haloalkyl;
R 2 is selected from the group consisting of 3 to 12 membered cycloalkyl, C-linked 3 to 12 membered heterocycloalkyl and —C(R A2 )(C 1-6 (halo)alkyl) 2 , wherein R A2 is hydrogen, —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —SF 5 , —OSF 5 , C 1-12 alkylthio, C 1-12 alkoxy, C 1-12 alkylamino and C 1-12 dialkylamino; and wherein R 2 is optionally substituted 1 to 5 R 2-A substituents selected from the group consisting of C 1-12 alkyl, C 1-12 haloalkyl, C 1-12 heteroalkyl, C 2-12 alkenyl, C 2-12 alkynyl, —F, —Cl, —Br, —I, —(X 2 ) 0-1 —CN, —(X 2 ) 0-1 —NO 2 , —(X 2 ) 0-1 —SF 5 , —(X 2 ) 0-1 —OSF 5 , —(X 2 ) 0-1 —OR 2A , —(X 2 ) 0-1 —N(R 2A ) 2 , —(X 2 ) 0-1 —SR 2A , —(X 2 ) 0-1 —CF 3 , 3 to 12 membered cycloalkyl-(X 2 ) 0-1 —, 3 to 12 membered heterocycloalkyl-(X 2 ) 0-1 —, 5 to 6 membered heteroaryl-(X 2 ) 0-1 —, phenyl-(X 2 ) 0-1 —, —(X 2 ) 0-1 —C(═O)N(R 2A )(R 2A ), —(X 2 ) 0-1 —C(═O)OR 2A , —(X 2 ) 0-1 —N(R 2A )C(═O)(R 2A ), —(X 2 ) 0-1 —N(R 2A )C(═O)OR 2A , —(X 2 ) 0-1 —S(═O) 1-2 —R 2A , —(X 2 ) 0-1 —N(R 2A )S(═O) 1-2 —R 2A , —(X 2 ) 0-1 —S(═O) 1-2 N(R 2A ) 2 , —(X 2 ) 0-1 —C(═O)R 2A , —(X 2 ) 0-1 —C(═NOR 2A )R 2A , —(X 2 ) 0-1 —N(R 2A )C(═O)N(R 2A ) 2 and —(X 2 ) 0-1 —OC(═O)R 2A , —(X 2 ) 0-1 —OP(═O)(OR 2A ) 2 , —(X 2 )—SC(═O)OR 2A and —(X 2 )—SC(═O)N(R 2A ) 2 ; wherein X 2 is selected from the group consisting of C 1-4 alkylene, C 1-4 haloalkylene, C 1-4 heteroalkylene, C 2-4 alkenylene, and C 2-4 alkynylene, R 2A at each occurrence is each independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, 3-7 membered cycloalkyl, 3-7 membered cycloalkyl-C 1-4 alkyl, 3-7 membered heterocycloalkyl, 3-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl, 5-6 membered heteroaryl-C 1-4 alkyl, phenyl and phenyl-C 1-4 alkyl, or any two R 2A groups attached to the same nitrogen atom are optionally combined to form a 3 to 6 membered heterocyclic ring comprising 1 to 2 additional heteroatom selected from N, O and S; and wherein a R 2-A substituent at each occurrence is independently optionally further substituted with 1 to 5 R 2A-1 substituents selected from the group consisting of —F, —Cl, —Br, —I, —OH, —CN, —NO 2 , —SF 5 , —NH 2 , C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 dialkylamino;
R 3 is selected from the group consisting of C 1-12 alkyl-, C 1-12 haloalkyl-, C 1-12 heteroalkyl-(L) 0-1 -, C 2-12 alkenyl-(L) 0-1 -, C 2-12 alkynyl-(L) 0-1 -, 3 to 12 membered cycloalkyl-(L) 0-1 -, 3 to 12 membered heterocycloalkyl-(L) 0-1 -, wherein L is selected from the group consisting of C 1-4 alkylene, C 1-4 haloalkylene, C 1-4 heteroalkylene, C 2-4 alkenylene, C 2-4 alkynylene, —C(═O)—, —C(═O)—N(H)—, —C(═O)N(C 1-6 alkyl)-, —C(═O)O—, —S(O) 1-2 — and —S(O) 1-2 —N(H)—; wherein a R 3 group is optionally further substituted with 1 to 5 R 3A substituents selected from the group consisting of —F, —Cl, —Br, —I, —OH, —CN, —NO 2 , —SF 5 , —OSF 5 , —NH 2 , C 1-6 alkyl, C 1-6 haloalkyl, 3 to 5 membered cycloalkyl, 3 to 5 membered heterocycloalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino and C 1-6 dialkylamino;
R 4 is selected from the group consisting of C 1-12 alkyl, C 1-12 haloalkyl, C 2-12 alkenyl, C 2-12 alkynyl, —F, —Cl, —Br, —I, —(X 4 ) 0-1 —CN, —(X 4 ) 0-1 —NO 2 , —(X 4 ) 0-1 —SF 5 , —(X 4 ) 0-1 —OSF 5 , —(X 4 ) 0-1 —OR 4A , —(X 4 ) 0-1 —N(R 4A ) 2 , —(X 4 ) 0-1 —SR 4A , —(X 4 ) 0-1 —CF 3 , 3 to 7 membered cycloalkyl-(X 4 ) 0-1 —, 3 to 7 membered heterocycloalkyl-(X 4 ) 0-1 —, 5 to 6 membered heteroaryl-(X 4 ) 0-1 —, phenyl-(X 4 ) 0-1 —, —(X 4 ) 0-1 —C(═O)N(R 4A )(R 4A ), —(X 4 ) 0-1 —C(═O)OR 4A , —(X 4 ) 0-1 —N(R 4A )C(═O)(R 4A ), —(X 4 ) 0-1 —N(R 4A )C(═O) OR 4A , —(X 4 ) 0-1 —S(═O) 1-2 —R 4A , —(X 4 ) 0-1 —N(R 4A )S(═O) 1-2 —R 4A , —(X 4 ) 0-1 —S(═O) 1-2 N(R 4A ) 2 , —(X 4 ) 0-1 —C(═O)R 4A , —(X 4 ) 0-1 —C(═NOR 4A )R 4A , —(X 4 ) 0-1 —N(R 4A )C(═O)N(R 4A ) 2 , —(X 4 ) 0-1 —OC(═O)R 4A , —(X 4 ) 0-1 —OP(═O)(OR 4A ) 2 , —(X 4 )—SC(═O)OR 4A and —(X 4 )—SC(═O)N(R 4A ) 2 , X 4 is selected from the group consisting of C 1-4 alkylene, C 1-4 haloalkylene, C 1-4 heteroalkylene, C 2-4 alkenylene, and C 2-4 alkynylene, R 4A at each occurrence is each independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl and C 1-6 heteroalkyl, or any two R 4A groups attached to the same nitrogen atom are optionally combined to form a 3 to 6 membered heterocyclic ring comprising 1 to 2 additional heteroatom selected from N, O and S; and wherein a R 4 group is independently optionally further substituted with 1 to 5 R 4A-1 substituents selected from the group consisting of —F, —Cl, —Br, —I, —OH, —CN, —NO 2 , —SF 5 , —NH 2 , C 1-6 alkoxy, C 1-6 alkylamino and C 1-6 dialkylamino;
R 5 and R 6 are each independently selected from the group consisting of hydrogen, C 1-12 alkyl, and C 1-12 haloalkyl; and
in the alternative R 4 and R 5 are combined to form a 5 to 7 membered heteroaryl or 5 to 7 membered heterocycloalkyl ring optionally comprising 1 additional heteroatom selected from N, O and S, and wherein said 5 to 7 membered heteroaryl or 5 to 7 membered heterocycloalkyl ring is further optionally substituted with 1 to 3 R 4/5cy substituents selected from the group consisting of C 1-12 alkyl, C 1-12 haloalkyl, C 2-12 alkenyl, C 2-12 alkynyl, —F, —Cl, —Br, —I, —(X 4/5 ) 0-1 —CN, —(X 4/5 ) 0-1 —NO 2 , —(X 4/5 ) 0-1 —SF 5 , —(X 4/5 ) 0-1 —OSF 5 , —(X 4/5 ) 0-1 —OR 45A , —(X 4/5 ) 0-1 —N(R 45A ) 2 , —(X 4/5 ) 0-1 —SR 45A , —(X 4/5 ) 0-1 —CF 3 , 3 to 12 membered cycloalkyl-(X 45 ) 0-1 —, 3 to 12 membered heterocycloalkyl-(X 4/5 ) 0-1 —, 5 to 6 membered heteroaryl-(X 4/5 ) 0-1 —, phenyl-(X 4/5 ) 0-1 —, —(X 4/5 ) 0-1 —C(═O)N(R 45A )(R 45A ), —(X 4/5 ) 0-1 —C(═O)OR 45A ,—(X 4/5 ) 0-1 —N(R 45A )C(═O)(R 45A ), —(X 4/5 ) 0-1 —N(R 45A )C(═O)OR 45A , —(X 4/5 ) 0-1 —S(═O) 1-2 —R 45A , —(X 4/5 ) 0-1 —N(R 45A )S(═O) 1-2 —R 45A , —(X 4/5 ) 0-1 —S(═O) 1-2 N(R 45A ) 2 , —(X 4/5 ) 0-1 —C(═O)R 45A , —(X 4/5 ) 0-1 —C(═NOR 45A )R 45A , —(X 4/5 ) 0-1 —N(R 45A )C(═O)N(R 45A ) 2 and —(X 4/5 ) 0-1 —OC(═O)R 45A , —(X 4/5 ) 0-1 —OP(═O)(OR 45A ) 2 , —(X 4/5 )—SC(═O)OR 45A and —(X 4/5 )—SC(═O)N(R 45A ) 2 , X 4/5 is selected from the group consisting of C 1-4 alkylene, C 1-4 haloalkylene, C 1-4 heteroalkylene, C 2-4 alkenylene, and C 2-4 alkynylene, R 45A at each occurrence is each independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl and C 1-6 heteroalkyl; or any two R 45A groups attached to the same nitrogen atom are optionally combined to form a 3 to 6 membered heterocyclic ring comprising 1 to 2 additional heteroatom selected from N, O and S; and wherein a R 4/5cy substituent at each occurrence is independently optionally further substituted with 1 to 5 R 4/5cy-1 substituents selected from the group consisting of —F, —Cl, —Br, —I, —OH, —CN, —NO 2 , —SF 5 , —NH 2 , C 1-6 alkoxy, C 1-6 alkylamino and C 1-6 dialkylamino; and
R 7 is hydrogen, or in the alternative R 4 and R 7 are optionally combined to form a 5 to 7 membered heteroaryl or 5 to 7 membered heterocycloalkyl ring optionally comprising 1 additional heteroatom selected from N, O and S.
2. The method of claim 1 , wherein R 5 and R 6 are each H.
3. The method of claim 1 , wherein R 4 is selected from the group consisting of C 1-12 alkyl, C 1-12 haloalkyl, —F, —Cl, —(X 4 ) 0-1 —CN, —(X 4 ) 0-1 —OR 4A , —(X 4 ) 0-1 —SR 4A , 3 to 7 membered cycloalkyl-(X 4 ) 0-1 —, —(X 4 ) 0-1 —S(═O) 1-2 —R 4A and is further optionally substituted.
4. The method of claim 1 , wherein R 4 is selected from the group consisting of —F, —Cl, C 1-4 alkyl, C 1-4 haloalkyl, —(C 1-4 alkylene) 0-1 -CN, C 1-4 alkyloxy, C 1-4 haloalkyloxy, C 1-4 alkylthio, C 1-4 haloalkylthio, 3 to 5 membered cycloalkyl-(C 1-4 alkyloxy)-, 3 to 6 membered cycloalkyl, and (C 1-4 alkyl)-S(O) 2 —, wherein R 4 is further optionally substituted.
5. The method of claim 1 , wherein R 4 is selected from the group consisting of —F, Cl, —CN, methyl, monofluoromethyl, difluoromethyl, trifluoromethyl, ethyl, 2-fluoroeth-1-yl, 1-fluoroeth-1-yl, 2,2-difluoroeth-1-yl, 1,2-difluoroeth-1-yl, 1,1-difluoroeth-1-yl, 2,2,2-trifluoroeth-1-yl, 1,2,2-trifluoroeth-1-yl, 1,1,2-trifluoroeth-1-yl, methoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, 2-fluoroethan-1-oxy, 2,2-difluoroethan-1oxy, 1,2-difluoroethan-1-oxy, 1,1-difluoroethan-1-oxy, 2,2,2-trifluoroethan-1-oxy, 1,2,2-trifluoroethan-1-oxy, 1,1,2-trifluoroethan-1-oxy, isopropoxy, 1-fluoro-propan-2-oxy, 1,1-difluoro-propan-2-oxy, 1,3-difluoro-propan-2-oxy, 1,1,1-trifluoro-propan-2-oxy, 1,1,3-trifluoro-propan-2-oxy, 1,1,1,3,3,3-hexafluoro-propan-2-oxy, monofluoromethylthio, difluoromethylthio, trifluroromethylthio, cyclopropylmethoxy and cyclopropyl.
6. The method of claim 1 , wherein R 6 is H; and R 4 and R 5 are combined to form a 5 to 7 membered ring selected from the group consisting of pyrrole, imidazole, pyrazole, pyrrolidone, pyrrolidine, morpholine, piperdine and piperazine, wherein R 4 and R 5 combined are optionally substituted with 1 to 3 R 4/5cy substituents.
7. The method of claim 1 , wherein R 4/5cy is selected from the group consisting of C 1-12 alkyl, C 1-12 haloalkyl, —F, —Cl, —(X 4/5 ) 0-1 —CN, —(X 4/5 ) 0-1 —OR 45A , 3 to 7 membered cycloalkyl-(X 4/5 ) 0-1 —, —(X 4/5 ) 0-1 —S(═O) 1-2 —R 45A , wherein R 4/5cy is optionally substituted with 1 to 3 R 4/5cy-1 substituents.
8. The method of claim 1 , wherein R 4/5cy is selected from the group consisting of —F, —Cl, C 1-4 alkyl, C 1-4 haloalkyl, —(C 1-4 alkylene) 0-1 -CN, C 1-4 alkyloxy, C 1-4 haloalkyloxy, C 1-4 alkylthio, C 1-4 haloalkylthio, 3-6 membered cycloalkyl-(C 1-4 alkyloxy)-, 3 to 6 membered cycloalkyl, and (C 1-4 alkyl)-S(O) 2 —, wherein R 4/5cy is optionally substituted with 1 to 5 R 4/5cy-1 substituents.
9. The method of claim 1 , wherein R 4/5cy is selected from the group consisting of —F, Cl, —CN, methyl, monofluoromethyl, difluoromethyl, trifluoromethyl, ethyl, 2-fluoroeth-1-yl, 1-fluoroeth-1-yl, 2,2-difluoroeth-1-yl, 1,2-difluoroeth-1-yl, 1,1-difluoroeth-1-yl, 2,2,2-trifluoroeth-1-yl, 1,2,2-trifluoroeth-1-yl, 1,1,2-trifluoroeth-1-yl, methoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, 2-fluoroethan-1-oxy, 2,2-difluoroethan-1oxy, 1,2-difluoroethan-1-oxy, 1,1-difluoroethan-1-oxy, 2,2,2-trifluoroethan-1-oxy, 1,2,2-trifluoroethan-1-oxy, 1,1,2-trifluoroethan-1-oxy, isopropoxy, 1-fluoro-propan-2-oxy, 1,1-difluoro-propan-2-oxy, 1,3-difluoro-propan-2-oxy, 1,1,1-trifluoro-propan-2-oxy, 1,1,3-trifluoro-propan-2-oxy, 1,1,1,3,3,3-hexafluoro-propan-2-oxy, monofluoromethylthio, difluoromethylthio, trifluroromethylthio, cyclopropylmethoxy and cyclopropyl.
10. The method of claim 1 , wherein R 1 is selected from the group consisting of hydrogen, C 1-4 alkyl and C 1-4 haloalkyl.
11. The method of claim 1 , wherein R 1 is hydrogen, monofluoromethyl, difluoromethyl, trifluormethyl and methyl.
12. The method of claim 1 , wherein R 1 is hydrogen.
13. The method of claim 1 , wherein R 2 is a fused or bridged 3 to 12 membered cycloalkyl or a fused or bridged bicyclic or tricyclic C-linked 3 to 12 membered heterocycloalkyl ring, wherein R 2 is optionally substituted with 1-5 R 2-A substituents.
14. The method of claim 1 , wherein R 2 is selected from the group consisting of 3-azabicyclo[3.1.0]hexane, 3-azabicyclo[3.2.1]octane, 3-azabicyclo[3.1.1]heptane, 1,1a,5,5a-tetrahydro-4a-aza-cyclopropa[a]pentalene, 1,1a,5,5a-tetrahydro-2,4a-diaza-cyclopropa[a]pentalene, 1,1a,5,5a-tetrahydro-3,4a-diaza-cyclopropa[a]pentalene, 1,1a,5,5a-tetrahydro-2,3,4a-triaza-cyclopropa[a]pentalene, 1,1a,5,5a-tetrahydro-4,4a-diaza-cyclopropa[a]pentalene, octahydro-4a-aza-cyclopropa[a]pentalene, 3-oxabicyclo[3.2.1]octane, 3-oxabicyclo[3.1.1]heptane and 3-oxabicyclo[3.1.0]hexane, and wherein R 2 is optionally substituted with 1 to 5 R 2-A substituents.
15. The method of claim 1 , wherein R 2 is selected from the group consisting of
16. The method of claim 1 , wherein R 2 is selected from the group consisting of
17. The method of claim 1 , wherein R 2 is a monocyclic ring, wherein R 2 is optionally substituted with 1 to 5 R 2-A substituents.
18. The method of claim 1 , wherein R 2 is a monocyclic ring selected from the group consisting of azetidine, pyrrolidine, pyrrolidone, piperidine, piperidone, azepane, azepanone, tetrahydrofuran, tetrahydrofuranone, tetrahydropyan, tetrahydropyanone, oxetane, oxetanone, oxepane and oxepanone, wherein R 2 is optionally substituted with 1 to 5 R 2-A substituents and wherein R 2-A is further optionally substituted.
19. The method of claim 1 , wherein R 2 is selected from the group consisting of
20. The method of claim 1 , wherein R 2-A is selected from the group consisting of C 1-12 alkyl, C 1-12 haloalkyl, C 1-12 heteroalkyl, —(X 2 ) 0-1 —CN, —(X 2 ) 0-1 —OR 2A , 3 to 12 membered cycloalkyl-(X 2 ) 0-1 —, 3 to 12 membered heterocycloalkyl-(X 2 ) 0-1 —, —(X 2 ) 0-1 —S(═O) 1-2 —R 2A and —(X 2 ) 0-1 —C(═O)R 2A , wherein R 2-A is optionally substituted.
21. The method of claim 1 , wherein R 2-A is selected from the group consisting of OH, (C 1-6 alkyl)-C(═O)—, (C 1-6 alkyl)-S(═O) 2 —, oxepane, azetidine, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl and —(C 1-6 alkyl)-CN, wherein R 2-A is optionally substituted.
22. The method of claim 1 , wherein R 2-A is selected from the group consisting of CH 3 —C(═O)—, oxetanyl, methyl, monofluoromethyl, difluoromethyl, trifluoromethyl, ethyl, 2-fluoroeth-1-yl, 1-fluoroeth-1-yl, 1,2-difluoroeth-1-yl, 2,2-difluoroeth-1-yl, 1,1,2-trifluoroeth-1-yl 2,2,2-trifluoroeth-1-yl, 1,2,2-trifluoroeth-1-yl, cyanomethyl, cyanoethyl, methoxyethyl, hydroxy, (CH 3 ) 2 (OH)CC(H) 2 —, CH 3 OCH 2 C(H)(CH 3 )—, CH 3 OC(CH 3 ) 2 CH 2 —, NCC(H)(CH 3 )CH 2 —, NCC(H)(CH 3 ) 2 CH 2 —, CH 3 OC(H)(CH 3 )CH 2 —, NCCH 2 C(H)(CH 3 )—, NCCCH 2 C(CH 3 ) 2 —, CH 3 —S(O) 2 — and isopropyl-OC(═O)—.
23. The method of claim 1 , wherein R 2 is —C(R A2 )(C 1-6 alkyl) 2 , wherein R A2 is hydrogen, —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —SF 5 , —OSF 5 , C 1-4 alkylthio, C 1-4 alkoxy, C 1-4 alkylamino and C 1-4 dialkylamino and wherein R 2 is optionally substituted with 1 to 5 R 2-A substituents.
24. The method of claim 1 , wherein R 3 is selected from the group consisting of C 1-6 alkyl, 3 to 6 membered cycloalkyl-C 1-4 alkyl, 3 to 6 membered cycloalkyl, 3 to 6 membered heterocycloalkyl-C 1-4 alkyl, and 3-6 membered heterocycloalkyl, wherein R 3 is optionally substituted with R 3A .
25. The method of claim 1 , wherein R 3 is selected from the group consisting of methyl, monofluoromethyl, difluoromethyl, ethyl, 1,1,1-trifluoroeth-2-yl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclobutylmethyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cyclohexylmethyl, 1,1-difluorocyclobut-3-yl, 1,1-difluorocyclopent-3-yl, oxetan-2-yl, oxetan-2-yl-methyl, oxetan-3-yl, oxetan-3-yl-methyl, tetrahydrofuran-3-yl, tetrahydrofuran-3-yl-methyl, tetrahydropyran-3-yl, tetrahydropyran-3-yl-methyl, tetrahydropyran-4-yl, tetrahydropyran-4-yl-methyl, azetindin-3-yl, azetindin-3-yl-methyl, pyrrolidin-3-yl, pyrrolidin-3-yl-methyl, piperidin-4yl, piperidin-4-yl-methyl, piperidin-3-yl and piperidin-3-yl-methyl.
26. The method of claim 1 , wherein said compound has a formula selected from the group consisting of:
27. The method of claim 1 , wherein said compound has the formula selected from the group consisting of
wherein in formula III-a, III-b, III-c, III-d, III-e, III-f and III-g, X H1 and X H2 at each occurrence is independently selected from the group consisting of N, NH, N(R 4/5cy ), CH or C(R 4/5cy ).
28. The method of claim 27 , wherein X H1 and X H2 are independently CH or C(R 4/5cy ).
29. The method of claim 1 , wherein said compound of Formula (I) is selected from the group consisting of
5-(5-isopropyl-1-(1-(oxetan-3-yl)azetidin-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
2-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)propan-2-ol,
2-(3-(6-amino-5-(difluoromethoxy)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)propan-2-ol,
2-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)-2-methylpropanenitrile,
2-(3-(6-amino-5-(difluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)-2-methylpropanenitrile,
2-(3-(6-amino-5-(trifluoromethoxy)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)-2-methylpropanenitrile,
5-(1-isopropyl-5-(1-methylazetidin-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
1-(3-(1-(cyclopropylmethyl)-3-(3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)azetidin-1-yl)ethanone,
1-(3-(1-(cyclopropylmethyl)-3-(3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)azetidin-1-yl)ethanone,
1-(3-(1-isopropyl-3-(3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)azetidin-1-yl)ethanone,
1-(3-(1-methyl-3-(3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)azetidin-1-yl)ethanone,
1-(3-(1-isopropyl-3-(3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-H-pyrazol-5-yl)azetidin-1-yl)ethanone,
racemic-5-(1-(cyclopropylmethyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(1-(3,3-difluorocyclopentyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(1,5-bis(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine
5-(1-(3,3-difluorocyclopentyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
(R)-5-(1-(cyclopropylmethyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
(S)-5-(1-(cyclopropylmethyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(1-(3,3-difluorocyclobutyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(1-(3,3-difluorocyclobutyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-ethyl-1H-pyrrolo[2,3-b]pyridine,
5-(1,5-bis(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-chloropyridin-2-amine,
5-(1,5-bis(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-fluoropyridin-2-amine,
3-chloro-5-(1-(3,3-difluorocyclopentyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-(3,3-difluorocyclopentyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-fluoropyridin-2-amine,
3-chloro-5-(1-(3,3-difluorocyclobutyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-((R)-tetrahydrofuran-3-yl)-5-((S)-tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-((R)-3,3-difluorocyclopentyl)-5-((R)-tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(5-((R)-tetrahydrofuran-3-yl)-1-((S)-tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(1,5-bis((S)-tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(1,5-bis((R)-tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-((S)-3,3-difluorocyclopentyl)-5-((S)-tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(1-((R)-3,3-difluorocyclopentyl)-5-((S)-tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(1-((S)-3,3-difluorocyclopentyl)-5-((R)-tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
1-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)cyclopentanol,
5-(1-(3,3-difluorocyclobutyl)-5-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(1-(3,3-difluorocyclobutyl)-5-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-3-yl)-3-ethyl-1H-pyrazolo[3,4-b]pyridine,
5-(1-(3,3-difluorocyclobutyl)-5-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-3-yl)-3-fluoropyridin-2-amine,
5-(1-(3,3-difluorocyclobutyl)-5-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
3-chloro-5-(1-(3,3-difluorocyclobutyl)-5-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-isopropyl-5-(1-methylpiperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-(1-methylpiperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
4-(1-(3,3-difluorocyclobutyl)-3-(3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)-1-methylpiperidin-2-one,
4-(3-(6-amino-5-chloropyridin-3-yl)-11-(3,3-difluorocyclobutyl)-1H-pyrazol-5-yl)-1-methylpiperidin-2-one,
4-(3-(6-amino-5-fluoropyridin-3-yl)-1-(3,3-difluorocyclobutyl)-1H-pyrazol-5-yl)-1-methylpiperidin-2-one,
4-(1-(3,3-difluorocyclobutyl)-3-(3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)-1-methylpiperidin-2-one,
5-(1-isopropyl-5-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile,
1-(4-(1-methyl-3-(3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)piperidin-1-yl)ethanone,
1-(4-(1-methyl-3-(3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)piperidin-1-yl)ethanone,
1-(4-(1-isopropyl-3-(3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)piperidin-1-yl)ethanone,
1-(4-(1-isopropyl-3-(3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)piperidin-1-yl)ethanone,
2-(4-(1-isopropyl-3-(3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)piperidin-1-yl)acetonitrile,
2-(4-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)piperidin-1-yl)acetonitrile,
5-(1-isopropyl-5-(1-(2-methoxyethyl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)azetidin-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(5-(1-(oxetan-3-yl)azetidin-3-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-(3,3-difluorocyclopentyl)-5-(1-(oxetan-3-yl)azetidin-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
3-chloro-5-(1-isopropyl-5-(1-(oxetan-3-yl)azetidin-3-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine,
3-fluoro-5-(1-isopropyl-5-(1-(oxetan-3-yl)azetidin-3-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)azetidin-3-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile,
5-(1-isopropyl-5-(1-(oxetan-3-yl)azetidin-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)azetidin-3-yl)-H-pyrazol-3-yl)-3, 3-dimethyl-1H-pyrrolo[2,3-b]pyridin-2(3H)-one,
6-(1-isopropyl-5-(1-(oxetan-3-yl)azetidin-3-yl)-1H-pyrazol-3-yl)-3H-imidazo[4,5-b]pyridine,
3-methyl-5-(1-methyl-5-(1-(oxetan-3-yl)pyrrolidin-3-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)pyrrolidin-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
3-chloro-5-(1-isopropyl-5-(1-(oxetan-3-yl)pyrrolidin-3-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine,
3-fluoro-5-(1-isopropyl-5-(1-(oxetan-3-yl)pyrrolidin-3-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)pyrrolidin-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-methyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
3-chloro-5-(1-cyclopentyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-chloro-5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one,
3-chloro-5-(5-(1-(oxetan-3-yl)piperidin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-fluoro-5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile,
3-chloro-5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
6-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3H-imidazo[4,5-b]pyridine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3,3-dimethyl-1H-pyrrolo[2,3-b]pyridin-2(3H)-one,
5-(1-cyclopentyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-methylpyridin-2-amine,
3-ethoxy-5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-isopropoxy-5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-(3,3-difluorocyclopentyl)-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-ethoxypyridin-2-amine,
5-(1-(3,3-difluorocyclopentyl)-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-isopropoxypyridin-2-amine,
3-(cyclopropylmethoxy)-5-(1-(3,3-difluorocyclopentyl)-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-cyclopentyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-methoxypyridin-2-amine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-methoxypyridin-2-amine,
5-(1-cyclopentyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-isopropoxypyridin-2-amine,
3-chloro-5-(1-(3,3-difluorocyclopentyl)-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
2-amino-5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)nicotinonitrile,
2-amino-5-(1-cyclopentyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)nicotinonitrile,
7-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine,
6-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-1,2,3,4-tetrahydro-1,8-naphthyridine,
5-(5-(1-(oxetan-3-yl)piperidin-4-yl)-1-(tetrahydrofuran-3-yl)-H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-cyclopropyl-5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-(difluoromethoxy)-5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-(3,3-difluorocyclopentyl)-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-methoxypyridin-2-amine,
5-(5-(1-cyclobutylpiperidin-4-yl)-1-isopropyl-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(5-(1-cyclobutylpiperidin-4-yl)-1-isopropyl-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-isopropyl-5-(4-methoxy-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(5-((1R,5S,6s)-3-oxabicyclo[3.1.0]hexan-6-yl)-1-isopropyl-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(5-((1R,5S,6s)-3-oxabicyclo[3.1.0]hexan-6-yl)-1-cyclopentyl-1H-pyrazol-3-yl)-3-chloropyridin-2-amine,
5-(5-((1R,5S,6s)-3-oxabicyclo[3.1.0]hexan-6-yl)-1-isopropyl-1H-pyrazol-3-yl)-3-fluoro-1H-pyrrolo[2,3-b]pyridine,
5-(5-((1R,5S,6r)-3-azabicyclo[3.1.0]hexan-6-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-isopropyl-5-((1R,5S,6r)-3-(methylsulfonyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine
5-(5-((1R,5S,6r)-3-(2,2-difluoroethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1-isopropyl-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-(difluoromethoxy)-5-(1-isopropyl-5-((1R,5S,6r)-3-(2,2,2-trifluoroethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-chloro-5-(1-(oxetan-3-yl)-5-((1R,5S,6r)-3-(2,2,2-trifluoroethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-chloro-5-(1-((3-methyloxetan-3-yl)methyl)-5-((1R,5S,6r)-3-(2,2,2-trifluoroethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
2-amino-5-(1-(cyclopropylmethyl)-5-((1R,5S,6r)-3-(2,2,2-trifluoroethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)nicotinonitrile,
7-(1-isopropyl-5-((1R,5S,6r)-3-(2,2,2-trifluoroethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-1H-pyrazolo[4,3-c]pyridin-4-amine,
1-((1R,5S,6r)-6-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)-3-azabicyclo[3.1.0]hexan-3-yl)ethanone,
3-chloro-5-(5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-isopropyl-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-chloro-5-(1-isopropyl-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-(difluoromethoxy)-5-(1-isopropyl-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-chloro-5-(1-isobutyl-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-chloro-5-(1-((2,2-difluorocyclopropyl)methyl)-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-(cyclopropylmethyl)-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-chloro-5-(1-(cyclopropylmethyl)-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-(cyclobutylmethyl)-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-isopropyl-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethoxy)pyridin-2-amine,
5-(5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-((1R,5S,6r)-6-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)-3-azabicyclo[3.1.0]hexan-3-yl)propanenitrile,
1-((1R,5S,6r)-6-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)-3-azabicyclo[3.1.0]hexan-3-yl)-2-methylpropan-2-ol,
5-(1-isopropyl-5-((1R,5S,6r)-3-(1-methoxypropan-2-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
(1R,5S,6r)-isopropyl 6-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)-3-azabicyclo[3.1.0]hexane-3-carboxylate,
3-((1R,5S,6r)-6-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)-3-azabicyclo[3.1.0]hexan-3-yl)butanenitrile,
5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile,
5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-chloro-5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(difluoromethoxy)pyridin-2-amine,
2-amino-5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)nicotinonitrile,
5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-cyclopropylpyridin-2-amine,
3-chloro-5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-(difluoromethoxy)-5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-cyclopropyl-5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine,
2-amino-5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)nicotinonitrile,
5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-methoxypyridin-2-amine,
3-isopropoxy-5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-chloro-5-(1-cyclobutyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-cyclobutyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-cyclobutyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-isopropoxypyridin-2-amine,
3-chloro-5-(5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-cyclobutyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(difluoromethoxy)pyridin-2-amine,
5-(1-(cyclopropylmethyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-cyclobutyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-cyclopropylpyridin-2-amine,
3-chloro-5-(1-(cyclopropylmethyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(methylsulfonyl)pyridin-2-amine,
5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-isopropoxypyridin-2-amine,
5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-methoxypyridin-2-amine,
3-(difluoromethyl)-5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-cyclobutyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-methoxypyridin-2-amine,
5-(1-(cyclobutylmethyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-cyclopropyl-5-(1-(cyclopropylmethyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-(cyclobutylmethyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-cyclopropylpyridin-2-amine,
5-(1-cyclobutyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethoxy)pyridin-2-amine,
5-(1-(cyclobutylmethyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(difluoromethoxy)pyridin-2-amine,
5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethoxy)pyridin-2-amine,
5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethoxy)pyridin-2-amine,
5-(1-(tert-butyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-cyclopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-(cyclopropylmethyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(difluoromethyl)pyridin-2-amine,
5-(1-cyclopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(difluoromethyl)pyridin-2-amine,
5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(difluoromethyl)pyridin-2-amine,
7-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-1H-pyrazolo[4,3-c]pyridin-4-amine,
5-(1-(cyclopropylmethyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(difluoromethoxy)pyridin-2-amine,
5-(5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-(1,1-difluoroethyl)-5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-(1,1-difluoroethoxy)-5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-((1-methylcyclopropyl)methyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(5-((1R,5S,6r)-3-cyclobutyl-3-azabicyclo[3.1.0]hexan-6-yl)-1-cyclopentyl-1H-pyrazol-3-yl)-3-(methylsulfonyl)pyridin-2-amine,
5-(1-isopropyl-5-(3-(oxetan-3-yl)-3-azabicyclo[3.1.1]heptan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-chloro-5-(1-isopropyl-5-(3-(oxetan-3-yl)-3-azabicyclo[3.1.1]heptan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-(difluoromethoxy)-5-(1-isopropyl-5-(3-(oxetan-3-yl)-3-azabicyclo[3.1.1]heptan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine, and
5-(1-isopropyl-5-(3-(oxetan-3-yl)-3-azabicyclo[3.1.1]heptan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethoxy)pyridin-2-amine,
and pharmaceutically acceptable salts thereof.
30. The method of claim 1 , wherein said neurodegenerative disease or condition is selected from the group consisting of: Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS).
31. The method of claim 1 , wherein the compound of Formula (I) is administered in combination with one or more additional pharmaceutical agents.
32. A method for inhibiting degeneration of a central nervous system (CNS) neuron or a portion thereof, the method comprising administering to the CNS neuron a compound of Formula (I)
or a salt thereof;
wherein in Formula (I)
R 1 is selected from the group consisting of hydrogen, —F, —Cl, —Br, —I, —NO 2 , —CN, C 1-12 alkyl and C 1-12 haloalkyl;
R 2 is selected from the group consisting of 3 to 12 membered cycloalkyl, C-linked 3 to 12 membered heterocycloalkyl and —C(R A2 )(C 1-6 (halo)alkyl) 2 , wherein R A2 is hydrogen, —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —SF 5 , —OSF 5 , C 1-12 alkylthio, C 1-12 alkoxy, C 1-12 alkylamino and C 1-12 dialkylamino; and wherein R 2 is optionally substituted 1 to 5 R 2-A substituents selected from the group consisting of C 1-12 alkyl, C 1-12 haloalkyl, C 1-12 heteroalkyl, C 2-12 alkenyl, C 2-12 alkynyl, —F, —Cl, —Br, —I, —(X 2 ) 0-1 —CN, —(X 2 ) 0-1 —NO 2 , —(X 2 ) 0-1 —SF 5 , —(X 2 ) 0-1 —OSF 5 , —(X 2 ) 0-1 —OR 2A , —(X 2 ) 0-1 —N(R 2A ) 2 , —(X 2 ) 0-1 —SR 2A , —(X 2 ) 0-1 —CF 3 , 3 to 12 membered cycloalkyl-(X 2 ) 0-1 —, 3 to 12 membered heterocycloalkyl-(X 2 ) 0-1 —, 5 to 6 membered heteroaryl-(X 2 ) 0-1 —, phenyl-(X 2 ) 0-1 —, —(X 2 ) 0-1 —C(═O)N(R 2A )(R 2A ), —(X 2 ) 0-1 —C(═O)OR 2A , —(X 2 ) 0-1 —N(R 2A )C(═O)(R 2A ), —(X 2 ) 0-1 —N(R 2A )C(═O)OR 2A , —(X 2 ) 0-1 —S(═O) 1-2 —R 2A , —(X 2 ) 0-1 —N(R 2A )S(═O) 1-2 —R 2A , —(X 2 ) 0-1 —S(═O) 1-2 N(R 2A ) 2 , —(X 2 ) 0-1 —C(═O)R 2A , —(X 2 ) 0-1 —C(═NOR 2A )R 2A , —(X 2 ) 0-1 —N(R 2A )C(═O)N(R 2A ) 2 and —(X 2 ) 0-1 —OC(═O)R 2A , —(X 2 ) 0-1 —OP(═O)(OR 2A ) 2 , —(X 2 )—SC(═O)OR 2A and —(X 2 )—SC(═O)N(R 2A ) 2 ; wherein X 2 is selected from the group consisting of C 1-4 alkylene, C 1-4 haloalkylene, C 1-4 heteroalkylene, C 2-4 alkenylene, and C 2-4 alkynylene, R 2A at each occurrence is each independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl, 3-7 membered cycloalkyl, 3-7 membered cycloalkyl-C 1-4 alkyl, 3-7 membered heterocycloalkyl, 3-7 membered heterocycloalkyl-C 1-4 alkyl, 5-6 membered heteroaryl, 5-6 membered heteroaryl-C 1-4 alkyl, phenyl and phenyl-C 1-4 alkyl, or any two R 2A groups attached to the same nitrogen atom are optionally combined to form a 3 to 6 membered heterocyclic ring comprising 1 to 2 additional heteroatom selected from N, O and S; and wherein a R 2-A substituent at each occurrence is independently optionally further substituted with 1 to 5 R 2A-1 substituents selected from the group consisting of —F, —Cl, —Br, —I, —OH, —CN, —NO 2 , —SF 5 , —NH 2 , C 1-6 alkoxy, C 1-6 alkylamino, C 1-6 dialkylamino;
R 3 is selected from the group consisting of C 1-12 alkyl-, C 1-12 haloalkyl-, C 1-12 heteroalkyl-(L) 0-1 -, C 2-12 alkenyl-(L) 0-1 -, C 2-12 alkynyl-(L) 0-1 -, 3 to 12 membered cycloalkyl-(L) 0-1 -, 3 to 12 membered heterocycloalkyl-(L) 0-1 -, wherein L is selected from the group consisting of C 1-4 alkylene, C 1-4 haloalkylene, C 1-4 heteroalkylene, C 2-4 alkenylene, C 2-4 alkynylene, —C(═O)—, —C(═O)—N(H)—, —C(═O)N(C 1-6 alkyl)-, —C(═O)O—, —S(O) 1-2 — and —S(O) 1-2 —N(H)—; wherein a R 3 group is optionally further substituted with 1 to 5 R 3A substituents selected from the group consisting of —F, —Cl, —Br, —I, —OH, —CN, —NO 2 , —SF 5 , —OSF 5 , —NH 2 , C 1-6 alkyl, C 1-6 haloalkyl, 3 to 5 membered cycloalkyl, 3 to 5 membered heterocycloalkyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino and C 1-6 dialkylamino;
R 4 is selected from the group consisting of C 1-12 alkyl, C 1-12 haloalkyl, C 2-12 alkenyl, C 2-12 alkynyl, —F, —Cl, —Br, —I, —(X 4 ) 0-1 —CN, —(X 4 ) 0-1 —NO 2 , —(X 4 ) 0-1 —SF 5 , —(X 4 ) 0-1 —OSF 5 , —(X 4 ) 0-1 —OR 4A , —(X 4 ) 0-1 —N(R 4A ) 2 , —(X 4 ) 0-1 —SR 4A , —(X 4 ) 0-1 —CF 3 , 3 to 7 membered cycloalkyl-(X 4 ) 0-1 —, 3 to 7 membered heterocycloalkyl-(X 4 ) 0-1 —, 5 to 6 membered heteroaryl-(X 4 ) 0-1 —, phenyl-(X 4 ) 0-1 —, —(X 4 ) 0-1 —C(═O)N(R 4A )(R 4A ), —(X 4 ) 0-1 —C(═O)OR 4A , —(X 4 ) 0-1 —N(R 4A )C(═O)(R 4A ), —(X 4 ) 0-1 —N(R 4A )C(═O) OR 4A , —(X 4 ) 0-1 —S(═O) 1-2 —R 4A , —(X 4 ) 0-1 —N(R 4A )S(═O) 1-2 —R 4A , —(X 4 ) 0-1 —S(═O) 1-2 —N(R 4A ) 2 , —(X 4 ) 0-1 —C(═O)R 4A , —(X 4 ) 0-1 —C(═NOR 4A )R 4A , —(X 4 ) 0-1 —N(R 4A )C(═O)N(R 4A ) 2 , —(X 4 ) 0-1 —OC(═O)R 4A , —(X 4 ) 0-1 —OP(═O)(OR 4A ) 2 , —(X 4 )—SC(═O)OR 4A and —(X 4 )—SC(═O)N(R 4A ) 2 , X 4 is selected from the group consisting of C 1-4 alkylene, C 1-4 haloalkylene, C 1-4 heteroalkylene, C 2-4 alkenylene, and C 2-4 alkynylene, R 4A at each occurrence is each independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl and C 1-6 heteroalkyl, or any two R 4A groups attached to the same nitrogen atom are optionally combined to form a 3 to 6 membered heterocyclic ring comprising 1 to 2 additional heteroatom selected from N, O and S; and wherein a R 4 group is independently optionally further substituted with 1 to 5 R 4A-1 substituents selected from the group consisting of —F, —Cl, —Br, —I, —OH, —CN, —NO 2 , —SF 5 , —NH 2 , C 1-6 alkoxy, C 1-6 alkylamino and C 1-6 dialkylamino;
R 5 and R 6 are each independently selected from the group consisting of hydrogen, C 1-12 alkyl, and C 1-12 haloalkyl; and
in the alternative R 4 and R 5 are combined to form a 5 to 7 membered heteroaryl or 5 to 7 membered heterocycloalkyl ring optionally comprising 1 additional heteroatom selected from N, O and S, and wherein said 5 to 7 membered heteroaryl or 5 to 7 membered heterocycloalkyl ring is further optionally substituted with 1 to 3 R 4/5cy substituents selected from the group consisting of C 1-12 alkyl, C 1-12 haloalkyl, C 2-12 alkenyl, C 2-12 alkynyl, —F, —Cl, —Br, —I, —(X 4/5 ) 0-1 —CN, —(X 4/5 ) 0-1 —NO 2 , —(X 4/5 ) 0-1 —SF 5 , —(X 4/5 ) 0-1 —OSF 5 , —(X 4/5 ) 0-1 —OR 45A , —(X 4/5 ) 0-1 —N(R 45A ) 2 , —(X 4/5 ) 0-1 —SR 45A , —(X 4/5 ) 0-1 —CF 3 , 3 to 12 membered cycloalkyl-(X 4/5 ) 0-1 —, 3 to 12 membered heterocycloalkyl-(X 4/5 ) 0-1 —, 5 to 6 membered heteroaryl-(X 4/5 ) 0-1 —, phenyl-(X 4/5 ) 0-1 —, —(X 4/5 ) 0-1 —C(═O)N(R 45A )(R 45A ), —(X 4/5 ) 0-1 —C(═O)OR 45A , —(X 4/5 ) 0-1 —N(R 45A )C(═O)(R 45A ), —(X 4/5 ) 0-1 —N(R 45A )C(═O)OR 45A , —(X 4/5 ) 0-1 —S(═O) 1-2 —R 45A , —(X 4/5 ) 0-1 —N(R 45A )S(═O) 1-2 —R 45A , —(X 4/5 ) 0-1 —S(═O) 1-2 N(R 45A ) 2 , —(X 4/5 ) 0-1 —C(═O)R 45A , —(X 4/5 ) 0-1 —C(═NOR 45A )R 45A , —(X 4/5 ) 0-1 —N(R 45A )C(═O)N(R 45A ) 2 and —(X 4/5 ) 0-1 —OC(═O)R 45A , —(X 4/5 ) 0-1 —OP(═O)(OR 45A ) 2 , —(X 4/5 )—SC(═O)OR 45A and —(X 4/5 )—SC(═O)N(R 45A ) 2 , X 4/5 is selected from the group consisting of C 1-4 alkylene, C 1-4 haloalkylene, C 1-4 heteroalkylene, C 2-4 alkenylene, and C 2-4 alkynylene, R 45A at each occurrence is each independently selected from the group consisting of hydrogen, C 1-6 alkyl, C 1-6 haloalkyl and C 1-6 heteroalkyl; or any two R 45A groups attached to the same nitrogen atom are optionally combined to form a 3 to 6 membered heterocyclic ring comprising 1 to 2 additional heteroatom selected from N, O and S; and wherein a R 4/5cy substituent at each occurrence is independently optionally further substituted with 1 to 5 R 4/5cy-1 substituents selected from the group consisting of —F, —Cl, —Br, —I, —OH, —CN, —NO 2 , —SF 5 , —NH 2 , C 1-6 alkoxy, C 1-6 alkylamino and C 1-6 dialkylamino; and
R 7 is hydrogen, or in the alternative R 4 and R 7 are optionally combined to form a 5 to 7 membered heteroaryl or 5 to 7 membered heterocycloalkyl ring optionally comprising 1 additional heteroatom selected from N, O and S.
33. The method of claim 32 , wherein R 5 and R 6 are each H.
34. The method of claim 32 , wherein R 4 is selected from the group consisting of C 1-12 alkyl, C 1-12 haloalkyl, —F, —Cl, —(X 4 ) 0-1 —CN, —(X 4 ) 0-1 —OR 4A , —(X 4 ) 0-1 —SR 4A , 3 to 7 membered cycloalkyl-(X 4 ) 0-1 —, —(X 4 ) 0-1 —S(═O) 1-2 —R 4A and is further optionally substituted.
35. The method of claim 32 , wherein R 4 is selected from the group consisting of —F, —Cl, C 1-4 alkyl, C 1-4 haloalkyl, —(C 1-4 alkylene) 0-1 -CN, C 1-4 alkyloxy, C 1-4 haloalkyloxy, C 1-4 alkylthio, C 1-4 haloalkylthio, 3 to 5 membered cycloalkyl-(C 1-4 alkyloxy)-, 3 to 6 membered cycloalkyl, and (C 1-4 alkyl)-S(O) 2 —, wherein R 4 is further optionally substituted.
36. The method of claim 32 , wherein R 4 is selected from the group consisting of —F, Cl, —CN, methyl, monofluoromethyl, difluoromethyl, trifluoromethyl, ethyl, 2-fluoroeth-1-yl, 1-fluoroeth-1-yl, 2,2-difluoroeth-1-yl, 1,2-difluoroeth-1-yl, 1,1-difluoroeth-1-yl, 2,2,2-trifluoroeth-1-yl, 1,2,2-trifluoroeth-1-yl, 1,1,2-trifluoroeth-1-yl, methoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, 2-fluoroethan-1-oxy, 2,2-difluoroethan-1oxy, 1,2-difluoroethan-1-oxy, 1,1-difluoroethan-1-oxy, 2,2,2-trifluoroethan-1-oxy, 1,2,2-trifluoroethan-1-oxy, 1,1,2-trifluoroethan-1-oxy, isopropoxy, 1-fluoro-propan-2-oxy, 1,1-difluoro-propan-2-oxy, 1,3-difluoro-propan-2-oxy, 1,1,1-trifluoro-propan-2-oxy, 1,1,3-trifluoro-propan-2-oxy, 1,1,1,3,3,3-hexafluoro-propan-2-oxy, monofluoromethylthio, difluoromethylthio, trifluroromethylthio, cyclopropylmethoxy and cyclopropyl.
37. The method of claim 32 , wherein R 6 is H; and R 4 and R 5 are combined to form a 5 to 7 membered ring selected from the group consisting of pyrrole, imidazole, pyrazole, pyrrolidone, pyrrolidine, morpholine, piperdine and piperazine, wherein R 4 and R 5 combined are optionally substituted with 1 to 3 R 4/5cy substituents.
38. The method of claim 32 , wherein R 4/5cy is selected from the group consisting of C 1-12 alkyl, C 1-12 haloalkyl, —F, —Cl, —(X 4/5 ) 0-1 —CN, —(X 4/5 ) 0-1 —OR 45A , 3 to 7 membered cycloalkyl-(X 4/5 ) 0-1 —, —(X 4/5 ) 0-1 —S(═O) 1-2 —R 45A , wherein R 4/5cy is optionally substituted with 1 to 3 R 4/5cy-1 substituents.
39. The method of claim 32 , wherein R 4/5cy is selected from the group consisting of —F, —Cl, C 1-4 alkyl, C 1-4 haloalkyl, —(C 1-4 alkylene) 0-1 -CN, C 1-4 alkyloxy, C 1-4 haloalkyloxy, C 1-4 alkylthio, C 1-4 haloalkylthio, 3-6 membered cycloalkyl-(C 1-4 alkyloxy)-, 3 to 6 membered cycloalkyl, and (C 1-4 alkyl)-S(O) 2 —, wherein R 4/5cy is optionally substituted with 1 to 5 R 4/5cy-1 substituents.
40. The method of claim 32 , wherein R 4/5cy is selected from the group consisting of —F, Cl, —CN, methyl, monofluoromethyl, difluoromethyl, trifluoromethyl, ethyl, 2-fluoroeth-1-yl, 1-fluoroeth-1-yl, 2,2-difluoroeth-1-yl, 1,2-difluoroeth-1-yl, 1,1-difluoroeth-1-yl, 2,2,2-trifluoroeth-1-yl, 1,2,2-trifluoroeth-1-yl, 1,1,2-trifluoroeth-1-yl, methoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, 2-fluoroethan-1-oxy, 2,2-difluoroethan-1oxy, 1,2-difluoroethan-1-oxy, 1,1-difluoroethan-1-oxy, 2,2,2-trifluoroethan-1-oxy, 1,2,2-trifluoroethan-1-oxy, 1,1,2-trifluoroethan-1-oxy, isopropoxy, 1-fluoro-propan-2-oxy, 1,1-difluoro-propan-2-oxy, 1,3-difluoro-propan-2-oxy, 1,1,1-trifluoro-propan-2-oxy, 1,1,3-trifluoro-propan-2-oxy, 1,1,1,3,3,3-hexafluoro-propan-2-oxy, monofluoromethylthio, difluoromethylthio, trifluroromethylthio, cyclopropylmethoxy and cyclopropyl.
41. The method of claim 32 , wherein R 1 is selected from the group consisting of hydrogen, C 1-4 alkyl and C 1-4 haloalkyl.
42. The method of claim 32 , wherein R 1 is hydrogen, monofluoromethyl, difluoromethyl, trifluormethyl and methyl.
43. The method of claim 32 , wherein R 1 is hydrogen.
44. The method of claim 32 , wherein R 2 is a fused or bridged 3 to 12 membered cycloalkyl or a fused or bridged bicyclic or tricyclic C-linked 3 to 12 membered heterocycloalkyl ring, wherein R 2 is optionally substituted with 1-5 R 2-A substituents.
45. The method of claim 32 , wherein R 2 is selected from the group consisting of 3-azabicyclo[3.1.0]hexane, 3-azabicyclo[3.2.1]octane, 3-azabicyclo[3.1.1]heptane, 1,1a,5,5a-tetrahydro-4a-aza-cyclopropa[a]pentalene, 1,1a,5,5a-tetrahydro-2,4a-diaza-cyclopropa[a]pentalene, 1,1a,5,5a-tetrahydro-3,4a-diaza-cyclopropa[a]pentalene, 1,1a,5,5a-tetrahydro-2,3,4a-triaza-cyclopropa[a]pentalene, 1,1a,5,5a-tetrahydro-4,4a-diaza-cyclopropa[a]pentalene, octahydro-4a-aza-cyclopropa[a]pentalene, 3-oxabicyclo[3.2.1]octane, 3-oxabicyclo[3.1.1]heptane and 3-oxabicyclo[3.1.0]hexane, and wherein R 2 is optionally substituted with 1 to 5 R 2-A substituents.
46. The method of claim 32 , wherein R 2 is selected from the group consisting of
47. The method of claim 32 , wherein R 2 is selected from the group consisting of
48. The method of claim 32 , wherein R 2 is a monocyclic ring, wherein R 2 is optionally substituted with 1 to 5 R 2-A substituents.
49. The method of claim 32 , wherein R 2 is a monocyclic ring selected from the group consisting of azetidine, pyrrolidine, pyrrolidone, piperidine, piperidone, azepane, azepanone, tetrahydrofuran, tetrahydrofuranone, tetrahydropyan, tetrahydropyanone, oxetane, oxetanone, oxepane and oxepanone, wherein R 2 is optionally substituted with 1 to 5 R 2-A substituents and wherein R 2-A is further optionally substituted.
50. The method of claim 32 , wherein R 2 is selected from the group consisting of
51. The method of claim 32 , wherein R 2-A is selected from the group consisting of C 1-12 alkyl, C 1-12 haloalkyl, C 1-12 heteroalkyl, —(X 2 ) 0-1 —CN, —(X 2 ) 0-1 —OR 2A , 3 to 12 membered cycloalkyl-(X 2 ) 0-1 —, 3 to 12 membered heterocycloalkyl-(X 2 ) 0-1 —, —(X 2 ) 0-1 —S(═O) 1-2 —R 2A and —(X 2 ) 0-1 —C(═O)R 2A , wherein R 2-A is optionally substituted.
52. The method of claim 32 , wherein R 2-A is selected from the group consisting of OH, (C 1-6 alkyl)-C(═O)—, (C 1-6 alkyl)-S(═O) 2 —, oxepane, azetidine, C 1-6 alkyl, C 1-6 haloalkyl, C 1-6 heteroalkyl and —(C 1-6 alkyl)-CN, wherein R 2-A is optionally substituted.
53. The method of claim 32 , wherein R 2-A is selected from the group consisting of CH 3 —C(═O)—, oxetanyl, methyl, monofluoromethyl, difluoromethyl, trifluoromethyl, ethyl, 2-fluoroeth-1-yl, 1-fluoroeth-1-yl, 1,2-difluoroeth-1-yl, 2,2-difluoroeth-1-yl, 1,1,2-trifluoroeth-1-yl 2,2,2-trifluoroeth-1-yl, 1,2,2-trifluoroeth-1-yl, cyanomethyl, cyanoethyl, methoxyethyl, hydroxy, (CH 3 ) 2 (OH)CC(H) 2 —, CH 3 OCH 2 C(H)(CH 3 )—, CH 3 OC(CH 3 ) 2 CH 2 —, NCC(H)(CH 3 )CH 2 —, NCC(H)(CH 3 ) 2 CH 2 —, CH 3 OC(H)(CH 3 )CH 2 —, NCCH 2 C(H)(CH 3 )—, NCCCH 2 C(CH 3 ) 2 —, CH 3 —S(O) 2 — and isopropyl-OC(═O)—.
54. The method of claim 32 , wherein R 2 is —C(R A2 )(C 1-6 alkyl) 2 , wherein R A2 is hydrogen, —F, —Cl, —Br, —I, —CN, —OH, —NH 2 , —SF 5 , —OSF 5 , C 1-4 alkylthio, C 1-4 alkoxy, C 1-4 alkylamino and C 1-4 dialkylamino and wherein R 2 is optionally substituted with 1 to 5 R 2-A substituents.
55. The method of claim 32 , wherein R 3 is selected from the group consisting of C 1-6 alkyl, 3 to 6 membered cycloalkyl-C 1-4 alkyl, 3 to 6 membered cycloalkyl, 3 to 6 membered heterocycloalkyl-C 1-4 alkyl, and 3-6 membered heterocycloalkyl, wherein R 3 is optionally substituted with R 3A .
56. The method of claim 32 , wherein R 3 is selected from the group consisting of methyl, monofluoromethyl, difluoromethyl, ethyl, 1,1,1-trifluoroeth-2-yl, propyl, isopropyl, butyl, sec-butyl, tert-butyl, cyclopropyl, cyclopropylmethyl, cyclobutyl, cyclobutylmethyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cyclohexylmethyl, 1,1-difluorocyclobut-3-yl, 1,1-difluorocyclopent-3-yl, oxetan-2-yl, oxetan-2-yl-methyl, oxetan-3-yl, oxetan-3-yl-methyl, tetrahydrofuran-3-yl, tetrahydrofuran-3-yl-methyl, tetrahydropyran-3-yl, tetrahydropyran-3-yl-methyl, tetrahydropyran-4-yl, tetrahydropyran-4-yl-methyl, azetindin-3-yl, azetindin-3-yl-methyl, pyrrolidin-3-yl, pyrrolidin-3-yl-methyl, piperidin-4yl, piperidin-4-yl-methyl, piperidin-3-yl and piperidin-3-yl-methyl.
57. The method of claim 32 , wherein said compound has a formula selected from the group consisting of:
58. The method of claim 32 , wherein said compound has the formula selected from the group consisting of
wherein in formula III-a, III-b, III-c, III-d, III-e, III-f and III-g, X H1 and X H2 at each occurrence is independently selected from the group consisting of N, NH, N(R 4/5cy ), CH or C(R 4/5cy ).
59. The method of claim 58 , wherein X H1 and X H2 are independently CH or C(R 4/5cy ).
60. The method of claim 32 , wherein said compound of Formula (I) is selected from the group consisting of
5-(5-isopropyl-1-(1-(oxetan-3-yl)azetidin-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
2-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)propan-2-ol,
2-(3-(6-amino-5-(difluoromethoxy)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)propan-2-ol,
2-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)-2-methylpropanenitrile,
2-(3-(6-amino-5-(difluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)-2-methylpropanenitrile,
2-(3-(6-amino-5-(trifluoromethoxy)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)-2-methylpropanenitrile,
5-(1-isopropyl-5-(1-methylazetidin-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
1-(3-(1-(cyclopropylmethyl)-3-(3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)azetidin-1-yl)ethanone,
1-(3-(1-(cyclopropylmethyl)-3-(3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)azetidin-1-yl)ethanone,
1-(3-(1-isopropyl-3-(3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)azetidin-1-yl)ethanone,
1-(3-(1-methyl-3-(3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)azetidin-1-yl)ethanone,
1-(3-(1-isopropyl-3-(3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-H-pyrazol-5-yl)azetidin-1-yl)ethanone,
racemic-5-(1-(cyclopropylmethyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(1-(3,3-difluorocyclopentyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(1,5-bis(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine
5-(1-(3,3-difluorocyclopentyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
(R)-5-(1-(cyclopropylmethyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
(S)-5-(1-(cyclopropylmethyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(1-(3,3-difluorocyclobutyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(1-(3,3-difluorocyclobutyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-ethyl-1H-pyrrolo[2,3-b]pyridine,
5-(1,5-bis(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-chloropyridin-2-amine,
5-(1,5-bis(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-fluoropyridin-2-amine,
3-chloro-5-(1-(3,3-difluorocyclopentyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-(3,3-difluorocyclopentyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-fluoropyridin-2-amine,
3-chloro-5-(1-(3,3-difluorocyclobutyl)-5-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-((R)-tetrahydrofuran-3-yl)-5-((S)-tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-((R)-3,3-difluorocyclopentyl)-5-((R)-tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(5-((R)-tetrahydrofuran-3-yl)-1-((S)-tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(1,5-bis((S)-tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(1,5-bis((R)-tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-((S)-3,3-difluorocyclopentyl)-5-((S)-tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(1-((R)-3,3-difluorocyclopentyl)-5-((S)-tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(1-((S)-3,3-difluorocyclopentyl)-5-((R)-tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
1-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)cyclopentanol,
5-(1-(3,3-difluorocyclobutyl)-5-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(1-(3,3-difluorocyclobutyl)-5-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-3-yl)-3-ethyl-1H-pyrazolo[3,4-b]pyridine,
5-(1-(3,3-difluorocyclobutyl)-5-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-3-yl)-3-fluoropyridin-2-amine,
5-(1-(3,3-difluorocyclobutyl)-5-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
3-chloro-5-(1-(3,3-difluorocyclobutyl)-5-(tetrahydro-2H-pyran-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-isopropyl-5-(1-methylpiperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-(1-methylpiperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
4-(1-(3,3-difluorocyclobutyl)-3-(3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)-1-methylpiperidin-2-one,
4-(3-(6-amino-5-chloropyridin-3-yl)-1-(3,3-difluorocyclobutyl)-1H-pyrazol-5-yl)-1-methylpiperidin-2-one,
4-(3-(6-amino-5-fluoropyridin-3-yl)-1-(3,3-difluorocyclobutyl)-1H-pyrazol-5-yl)-1-methylpiperidin-2-one,
4-(1-(3,3-difluorocyclobutyl)-3-(3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)-1-methylpiperidin-2-one,
5-(1-isopropyl-5-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile,
1-(4-(1-methyl-3-(3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)piperidin-1-yl)ethanone,
1-(4-(1-methyl-3-(3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)piperidin-1-yl)ethanone,
1-(4-(1-isopropyl-3-(3-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)piperidin-1-yl)ethanone,
1-(4-(1-isopropyl-3-(3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)piperidin-1-yl)ethanone,
2-(4-(1-isopropyl-3-(3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl)-1H-pyrazol-5-yl)piperidin-1-yl)acetonitrile,
2-(4-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)piperidin-1-yl)acetonitrile,
5-(1-isopropyl-5-(1-(2-methoxyethyl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)azetidin-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(5-(1-(oxetan-3-yl)azetidin-3-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-(3,3-difluorocyclopentyl)-5-(1-(oxetan-3-yl)azetidin-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
3-chloro-5-(1-isopropyl-5-(1-(oxetan-3-yl)azetidin-3-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine,
3-fluoro-5-(1-isopropyl-5-(1-(oxetan-3-yl)azetidin-3-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)azetidin-3-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile,
5-(1-isopropyl-5-(1-(oxetan-3-yl)azetidin-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)azetidin-3-yl)-H-pyrazol-3-yl)-3, 3-dimethyl-1H-pyrrolo[2,3-b]pyridin-2(3H)-one,
6-(1-isopropyl-5-(1-(oxetan-3-yl)azetidin-3-yl)-1H-pyrazol-3-yl)-3H-imidazo[4,5-b]pyridine,
3-methyl-5-(1-methyl-5-(1-(oxetan-3-yl)pyrrolidin-3-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)pyrrolidin-3-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
3-chloro-5-(1-isopropyl-5-(1-(oxetan-3-yl)pyrrolidin-3-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine,
3-fluoro-5-(1-isopropyl-5-(1-(oxetan-3-yl)pyrrolidin-3-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)pyrrolidin-3-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-methyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-methyl-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
3-chloro-5-(1-cyclopentyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-chloro-5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridin-2(3H)-one,
3-chloro-5-(5-(1-(oxetan-3-yl)piperidin-4-yl)-1-(tetrahydrofuran-3-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-fluoro-5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile,
3-chloro-5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
6-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3H-imidazo[4,5-b]pyridine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3,3-dimethyl-1H-pyrrolo[2,3-b]pyridin-2(3H)-one,
5-(1-cyclopentyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-methylpyridin-2-amine,
3-ethoxy-5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-isopropoxy-5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-(3,3-difluorocyclopentyl)-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-ethoxypyridin-2-amine,
5-(1-(3,3-difluorocyclopentyl)-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-isopropoxypyridin-2-amine,
3-(cyclopropylmethoxy)-5-(1-(3,3-difluorocyclopentyl)-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-cyclopentyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-methoxypyridin-2-amine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-methoxypyridin-2-amine,
5-(1-cyclopentyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-isopropoxypyridin-2-amine,
3-chloro-5-(1-(3,3-difluorocyclopentyl)-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
2-amino-5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)nicotinonitrile,
2-amino-5-(1-cyclopentyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)nicotinonitrile,
7-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3,4-dihydro-2H-pyrido[3,2-b][1,4]oxazine,
5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine,
6-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-1,2,3,4-tetrahydro-1,8-naphthyridine,
5-(5-(1-(oxetan-3-yl)piperidin-4-yl)-1-(tetrahydrofuran-3-yl)-H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-cyclopropyl-5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-(difluoromethoxy)-5-(1-isopropyl-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-(3,3-difluorocyclopentyl)-5-(1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-methoxypyridin-2-amine,
5-(5-(1-cyclobutylpiperidin-4-yl)-1-isopropyl-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(5-(1-cyclobutylpiperidin-4-yl)-1-isopropyl-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-isopropyl-5-(4-methoxy-1-(oxetan-3-yl)piperidin-4-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(5-((1R,5S,6s)-3-oxabicyclo[3.1.0]hexan-6-yl)-1-isopropyl-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(5-((1R,5S,6s)-3-oxabicyclo[3.1.0]hexan-6-yl)-1-cyclopentyl-1H-pyrazol-3-yl)-3-chloropyridin-2-amine,
5-(5-((1R,5S,6s)-3-oxabicyclo[3.1.0]hexan-6-yl)-1-isopropyl-1H-pyrazol-3-yl)-3-fluoro-1H-pyrrolo[2,3-b]pyridine,
5-(5-((1R,5S,6r)-3-azabicyclo[3.1.0]hexan-6-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-isopropyl-5-((1R,5S,6r)-3-(methylsulfonyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine
5-(5-((1R,5S,6r)-3-(2,2-difluoroethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1-isopropyl-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-(difluoromethoxy)-5-(1-isopropyl-5-((1R,5S,6r)-3-(2,2,2-trifluoroethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-chloro-5-(1-(oxetan-3-yl)-5-((1R,5S,6r)-3-(2,2,2-trifluoroethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-chloro-5-(1-((3-methyloxetan-3-yl)methyl)-5-((1R,5S,6r)-3-(2,2,2-trifluoroethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
2-amino-5-(1-(cyclopropylmethyl)-5-((1R,5S,6r)-3-(2,2,2-trifluoroethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)nicotinonitrile,
7-(1-isopropyl-5-((1R,5S,6r)-3-(2,2,2-trifluoroethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-1H-pyrazolo[4,3-c]pyridin-4-amine,
1-((1R,5S,6r)-6-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)-3-azabicyclo[3.1.0]hexan-3-yl)ethanone,
3-chloro-5-(5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-isopropyl-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-chloro-5-(1-isopropyl-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-(difluoromethoxy)-5-(1-isopropyl-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-chloro-5-(1-isobutyl-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-chloro-5-(1-((2, 2-difluorocyclopropyl)methyl)-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-(cyclopropylmethyl)-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-chloro-5-(1-(cyclopropylmethyl)-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-(cyclobutylmethyl)-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-isopropyl-5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethoxy)pyridin-2-amine,
5-(5-((1R,5S,6r)-3-(2-methoxyethyl)-3-azabicyclo[3.1.0]hexan-6-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-((1R,5S,6r)-6-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)-3-azabicyclo[3.1.0]hexan-3-yl)propanenitrile,
1-((1R,5S,6r)-6-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)-3-azabicyclo[3.1.0]hexan-3-yl)-2-methylpropan-2-ol,
5-(1-isopropyl-5-((1R,5S,6r)-3-(1-methoxypropan-2-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
(1R,5S,6r)-isopropyl 6-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)-3-azabicyclo[3.1.0]hexane-3-carboxylate,
3-((1R,5S,6r)-6-(3-(6-amino-5-(trifluoromethyl)pyridin-3-yl)-1-isopropyl-1H-pyrazol-5-yl)-3-azabicyclo[3.1.0]hexan-3-yl)butanenitrile,
5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-1H-pyrrolo[2,3-b]pyridine-3-carbonitrile,
5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridine,
5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-chloro-5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(difluoromethoxy)pyridin-2-amine,
2-amino-5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)nicotinonitrile,
5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-cyclopropylpyridin-2-amine,
3-chloro-5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-(difluoromethoxy)-5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-cyclopropyl-5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3,3-dimethyl-2,3-dihydro-1H-pyrrolo[2,3-b]pyridine,
2-amino-5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)nicotinonitrile,
5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-methoxypyridin-2-amine,
3-isopropoxy-5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-chloro-5-(1-cyclobutyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-cyclobutyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-cyclobutyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-isopropoxypyridin-2-amine,
3-chloro-5-(5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-cyclobutyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(difluoromethoxy)pyridin-2-amine,
5-(1-(cyclopropylmethyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-cyclobutyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-cyclopropylpyridin-2-amine,
3-chloro-5-(1-(cyclopropylmethyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(methylsulfonyl)pyridin-2-amine,
5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-isopropoxypyridin-2-amine,
5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-methoxypyridin-2-amine,
3-(difluoromethyl)-5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-cyclobutyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-methoxypyridin-2-amine,
5-(1-(cyclobutylmethyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-cyclopropyl-5-(1-(cyclopropylmethyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-(cyclobutylmethyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-cyclopropylpyridin-2-amine,
5-(1-cyclobutyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethoxy)pyridin-2-amine,
5-(1-(cyclobutylmethyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(difluoromethoxy)pyridin-2-amine,
5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethoxy)pyridin-2-amine,
5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethoxy)pyridin-2-amine,
5-(1-(tert-butyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-cyclopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(1-(cyclopropylmethyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(difluoromethyl)pyridin-2-amine,
5-(1-cyclopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(difluoromethyl)pyridin-2-amine,
5-(1-cyclopentyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(difluoromethyl)pyridin-2-amine,
7-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-1H-pyrazolo[4,3-c]pyridin-4-amine,
5-(1-(cyclopropylmethyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(difluoromethoxy)pyridin-2-amine,
5-(5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1-(2,2,2-trifluoroethyl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-(1,1-difluoroethyl)-5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-(1,1-difluoroethoxy)-5-(1-isopropyl-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
5-(1-((1-methylcyclopropyl)methyl)-5-((1R,5S,6r)-3-(oxetan-3-yl)-3-azabicyclo[3.1.0]hexan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
5-(5-((1R,5S,6r)-3-cyclobutyl-3-azabicyclo[3.1.0]hexan-6-yl)-1-cyclopentyl-1H-pyrazol-3-yl)-3-(methylsulfonyl)pyridin-2-amine,
5-(1-isopropyl-5-(3-(oxetan-3-yl)-3-azabicyclo[3.1.1]heptan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethyl)pyridin-2-amine,
3-chloro-5-(1-isopropyl-5-(3-(oxetan-3-yl)-3-azabicyclo[3.1.1]heptan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine,
3-(difluoromethoxy)-5-(1-isopropyl-5-(3-(oxetan-3-yl)-3-azabicyclo[3.1.1]heptan-6-yl)-1H-pyrazol-3-yl)pyridin-2-amine, and
5-(1-isopropyl-5-(3-(oxetan-3-yl)-3-azabicyclo[3.1.1]heptan-6-yl)-1H-pyrazol-3-yl)-3-(trifluoromethoxy)pyridin-2-amine,
and salts thereof.
61. The method of claim 32 , wherein said administering to the CNS neuron is performed in vitro.
62. The method of claim 61 , wherein the method further comprises grafting or implanting the CNS neuron into a human patient after administration of the agent.
63. The method of claim 32 , wherein the CNS neuron is present in a human patient.
64. The method of claim 32 , wherein administering to the CNS neuron comprises administration of said compound of formula I in a pharmaceutically acceptable carrier, diluent or excipient.
65. The method of claim 32 , wherein administering to the CNS neuron is carried out by an administration route selected from the group consisting of parenteral, subcutaneous, intravenous, intraperitoneal, intracerebral, intralesional, intramuscular, intraocular, intraarterial interstitial infusion and implanted delivery device.
66. The method of claim 32 further comprising administering one or more additional pharmaceutical agents.
67. The method of claim 32 , wherein the administering of a compound of Formula (I) results in a decrease in JNK phosphorylation, JNK activity and/or JNK expression.
68. The method of claim 32 , wherein the administering of a compound of Formula (I) results in a decrease of cJun phosphorylation, cJun activity, and/or cJun expression.
69. The method of claim 32 , wherein the administering of a compound of Formula (I) results in a decrease in p38 phosphorylation, p38 activity, and/or p38 expression.Cited by (0)
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